MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells

Mir-205 plays an important role in epithelial biogenesis and in mammary gland development but its role in cancer still remains controversial depending on the specific cellular context and target genes. We have previously reported that miR-205-5p is upregulated in breast cancer stem cells targeting ERBB pathway and leading to targeted therapy resistance. Here we show that miR-205-5p regulates tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer results in reduced tumor growth and metastatic spreading in mouse models. Moreover, we show that miR-205-5p knock-down can be obtained with the use of specific locked nucleic acids oligonucleotides in vivo suggesting a future potential use of this approach in therapy

Impacto de los residuos de ivermectina en los procesos tecnológicos de la leche y sus derivados

Se evaluó la estabilidad química de los residuos de ivermectina (IVM, fármaco antiparasitario) en leches bovina y ovina. La estabilidad del fármaco se midió mediante cromatografía liquida de alta performance analizando muestras de leche con residuos de IVM antes y después del tratamiento térmico. Además se evaluó, mediante la prueba del yogur y estudios microbiológicos de recuento de bacterias lácticas, el efecto de los residuos sobre la viabilidad de las bacterias ácido lácticas. Los residuos de IVM en leche demostraron ser estables a los tratamientos térmicos utilizados en la industria láctea de pasteurización: baja temperatura/largo tiempo (LTLT 65ºC, 30 min) y alta temperatura/corto tiempo (HTST 75ºC, 15 s). Los procesos de industrialización de la leche basados en la actividad de las bacterias lácticas tampoco fueron afectados por la presencia de residuos de IVM. Las concentraciones evaluadas no modificaron el incremento de la acidez en la prueba del yogur y no disminuyeron los recuentos de bacterias lácticas presentes en muestras de yogures elaborados con residuos del antiparasitario. El impacto de los residuos de fármacos antiparasitarios en los procesos tecnológicos de elaboración de alimentos y en la salud del consumidor a largo plazo debe ser cuidadosamente analizado.Chemical stability of ivermectin residues (IVM, antiparasitic drug) in cattle and sheep milk was evaluated. IVM residues were measured in milk samples before and after heat treatment by high performance liquid chromatography. Additionally, the effect of drug residues on the lactic acid fermentation was assessed by testing the viability and counts of lactic acid bacteria. IVM concentrations in milk were stable after standard procedures used in dairy industry LTLT pasteurization (65°C, 30 min) and HTST (75°C, 15 s). Industrial milk processing based on the activity of lactic acid bacteria was not affected by the presence of IVM residues. IVM concentrations did not affect the increment of acidity nor the number of lactic acid bacteria in yogurt samples. The impact of the residues of antiparasitic drugs in technological processes of food processing and consumer health must be carefully analyzed to avoid long-term consequences

Congenital mirror movements in a new Italian family

Mirror movements (MMs) occur on the contralateral side of a limb being used intentionally. Because few families with congenital MMs and no other neurological signs have been reported, the underlying mechanisms of MMs are still not entirely clear. We report on the clinical, genetic, neurophysiological and neuroimaging findings of 10 of 26 living members of a novel four-generation family with congenital MMs. DCC and RAD51 were sequenced in affected members of the family. Five of the ten subjects with MMs underwent neurophysiological and neuroimaging evaluations. The neurophysiological evaluation consisted of electromyographic (EMG) mirror recordings, investigations of corticospinal excitability, and analysis of interhemispheric inhibition using transcranial magnetic stimulation techniques. The neuroimaging evaluation included functional MRI during finger movements. Eight (all females) of the ten members examined presented MMs of varying degrees at the clinical assessment. Transmission of MMs appears to have occurred according to an autosomal-dominant fashion with variable expression. No mutation in DCC or RAD51 was identified. EMG mirror activity was higher in MM subjects than in healthy controls. Short-latency interhemispheric inhibition was reduced in MM subjects. Ipsilateral motor-evoked potentials were detectable in the most severe case. The neuroimaging evaluation did not disclose any significant abnormalities in MM subjects. The variability of the clinical features of this family, and the lack of known genetic abnormalities, suggests that MMs are heterogeneous disorders. The pathophysiological mechanisms of MMs include abnormalities of transcallosal inhibition and corticospinal decussatio

Validity and Reliability of the Assessment of Quality of Life (AQoL)-8D Multi-Attribute Utility Instrument

OBJECTIVE: The purpose of this paper was to report tests of the validity and reliability of a new instrument, the Assessment of Quality of Life (AQoL)-8D, which was constructed to improve the evaluation of health services that have an impact upon the psychosocial aspects of the quality of life. METHODS: Australian and US data from a large multi-instrument comparison survey were used to conduct tests of convergent, predictive and content validity using as comparators five other multi-attribute utility (MAU) instruments—the EQ-5D, SF-6D, Health Utilities Index (HUI) 3, 15D and the Quality of Well-Being (QWB)—as well as four non-utility instruments—the SF-36 and three measures of subjective well-being (SWB). A separate three part Australian survey was used to assess test–retest reliability. RESULTS: Results indicate that AQoL-8D correlates more highly with both the SWB instruments and the psychosocial dimensions of the SF-36, and that it is similar to the other MAU instruments in terms of its convergent and predictive validity. The second Australian survey demonstrated high test–retest reliability. CONCLUSIONS: The results indicate that the AQoL-8D is a reliable and valid instrument which offers an alternative to the MAU instruments presently used in economic evaluation studies, and one which is particularly suitable when psychosocial elements of health are of importance

Construction of the descriptive system for the assessment of quality of life AQoL-6D utility instrument

BackgroundMulti attribute utility (MAU) instruments are used to include the health related quality of life (HRQoL) in economic evaluations of health programs. Comparative studies suggest different MAU instruments measure related but different constructs. The objective of this paper is to describe the methods employed to achieve content validity in the descriptive system of the Assessment of Quality of Life (AQoL)-6D, MAU instrument.MethodsThe AQoL program introduced the use of psychometric methods in the construction of health related MAU instruments. To develop the AQoL-6D we selected 112 items from previous research, focus groups and expert judgment and administered them to 316 members of the public and 302 hospital patients. The search for content validity across a broad spectrum of health states required both formative and reflective modelling. We employed Exploratory Factor Analysis and Structural Equation Modelling (SEM) to meet these dual requirements.Results and DiscussionThe resulting instrument employs 20 items in a multi-tier descriptive system. Latent dimension variables achieve sensitive descriptions of 6 dimensions which, in turn, combine to form a single latent QoL variable. Diagnostic statistics from the SEM analysis are exceptionally good and confirm the hypothesised structure of the model.ConclusionsThe AQoL-6D descriptive system has good psychometric properties. They imply that the instrument has achieved construct validity and provides a sensitive description of HRQoL. This means that it may be used with confidence for measuring health related quality of life and that it is a suitable basis for modelling utilities for inclusion in the economic evaluation of health programs.<br /

Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p &lt; 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p &lt; 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p &lt; 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Percutaneous thermal segmentectomy for liver malignancies over 3 cm: mid-term oncological performance and predictors of sustained complete response from a multicentric Italian retrospective study

Introduction: Percutaneous thermal segmentectomy is a single-step combination of microwave ablation, performed during arterial occlusion obtained with a balloon micro catheter, followed in the same session by balloon-occluded TACE. The aim of this multicenter retrospective study is to report the mid-term oncological performance of this technique for liver malignancies &gt; 3.0&nbsp;cm and to identify risk factors for the loss of sustained complete response. Methods: Oncological results were evaluated with CT or MRI according to m-RECIST (HCC) and RECISTv1.1 (metastasis/intra-hepatic cholangiocarcinoma, iCC) at 1-month, 3–6-month and then at regular-6-month intervals. To identify predictive variables associated with not achieving or losing complete response two mixed-effects multivariable logistic regression models were constructed. Results: Sixty-three patients (40/23, male/female) with primary liver malignancies (HCC = 49; iCC = 4) and metastasis (n = 10) were treated. Median diameter of target lesion was 4.5&nbsp;cm (range 3.0–7.0&nbsp;cm). The median follow-up time was 9.2&nbsp;months. At one-month follow-up, 79.4% of patients presented with a complete response and the remaining 20.6% were partial responders. At the 3–6-month follow-up, reached by 59 of the initial 63 patients, 83.3% showed a sustained complete response, while 10.2% had a partial response and 8.5% a local recurrence. At the last follow-up, 69.8% of the lesions showed a complete response. The initial diameter of the target lesion ≥ 5.0&nbsp;cm was the only independent variable associated with the risk of failure in maintaining a complete response at 6&nbsp;months (OR = 8.58, 95% CI 1.38–53.43; P = 0.02). Conclusion: Percutaneous thermal segmentectomy achieves promising oncological results in patients with tumors &gt; 3.0&nbsp;cm, with tumor dimension ≥ 5.0&nbsp;cm being the only risk factor associated with the failure of a sustained complete response